Coronary plaque progression of non-culprit lesions after culprit percutaneous coronary intervention in patients with moderate to advanced chronic kidney disease: intravascular ultrasound and integrated backscatter intravascular ultrasound study.

Previous studies have suggested that the deterioration of renal function increases the risk of major adverse clinical events not only in culprit lesions but also in non-culprit lesions (NCLs) after percutaneous coronary intervention (PCI). This study evaluated serial coronary plaque change of NCL in patients with different stages of chronic kidney disease (CKD) using intravascular ultrasound (IVUS) and integrated backscatter IVUS (IB-IVUS). In 113 patients (113 NCLs) underwent both IVUS-guided PCI and follow-up IVUS, volumetric IVUS analyses were performed at proximal reference NCLs in de novo target vessels post PCI and at 8-month follow-up. NCLs were divided into 4 groups based on baseline CKD stage: CKD-1, n = 18; CKD-2, n = 42; CKD-3, n = 29; and CKD4-5, n = 24. We compared serial changes of plaque burden and composition among groups under statin treatment. Plaque progression occurred in CKD-3 (+4.6 mm(3), p < 0.001) and CKD4-5 (+9.8 mm(3), p < 0.001) despite anti-atherosclerotic treatment, whereas plaque regression occurred in CKD-1 (-5.4 mm(3), p = 0.002) and CKD-2 (-3.2 mm(3), p = 0.001) mainly due to initiate statin treatment after PCI. Plaque volume change was correlated with eGFR (p < 0.0001). Multivariate analysis showed CKD stage 3-5 was an independent predictor of plaque progression. Regarding IB-IVUS analyses, lipid plaque increased in CKD-3 (+4.6 mm(3), p < 0.001) and CKD4-5 (+5.4 mm(3), p < 0.001), but decreased in CKD-2 (-2.7 mm(3), p < 0.05). Fibrotic plaque also increased in CKD4-5 (+3.4 mm(3), p < 0.001). Moderate to advanced CKD was associated with coronary plaque progression characterized by greater lipid and fibrotic plaque volumes in NCL under statin treatment after culprit PCI.

Press-through package mis-swallowing: Usefulness of computed tomography.

Case: An 88-year-old female with Alzheimer's-type dementia who mis-swallowed a press-through package visited our emergency department. Outcome: Plain radiography detected no foreign bodies, whereas plain computed tomography showed an elliptical body with a high density in the lower esophagus. The press-through package containing a tablet in the esophagogastric junction was successfully removed without severe complications using the endoscopic protector hood. In cases of press-through package mis-swallowing, it is important for emergency physicians to make an early and correct diagnosis of the location of the package, which shows high radiolucency. Based on the results of this case, we hypothesize that carrying out early computed tomography examinations is useful for identifying swallowed press-through packages. Our retrospective investigation showed that computed tomography has a sensitivity of 100% for detecting press-through packages. Conclusion: We experienced a case of press-through package mis-swallowing diagnosed on computed tomography. We recommend performing computed tomography examinations, especially in patients with an uncertain history and unclear symptoms.

Plasma levels of nitric oxide metabolites are markedly reduced in normotensive men with electrocardiographically determined left ventricular hypertrophy.

Recent studies have revealed that electrocardiographically determined left ventricular hypertrophy (ECG-LVH) is a risk factor for cardiovascular death not only in hypertensive patients but also in normotensive subjects. However, the underlying mechanisms remain to be elucidated. In this study, we tested our hypothesis that normotensive subjects with ECG-LVH have reduced nitric oxide production. A total of 840 Japanese male workers were enrolled, and 579 eligible subjects were studied. ECG-LVH was assessed according to the Sokolow-Lyon voltage criteria and the Cornell voltage-duration product. The median level of plasma NOx (nitrite plus nitrate), a marker of systemic nitric oxide production, was markedly lower in the normotensive subjects with ECG-LVH (n=73) than in those without (n=506), and the clinical characteristics were significantly different between the 2 groups (each P<0.05). Importantly, a one-to-one propensity score matching analysis showed similar markedly lower median plasma NOx level in the normotensive subjects with ECG-LVH compared with that observed in the matched normotensive subjects without ECG-LVH (P<0.05). Furthermore, the tertiles of the plasma NOx levels were inversely correlated with the prevalence and severity of ECG-LVH (both P<0.05). The lower plasma NOx levels were associated with significantly higher plasma 8-isoprostane levels, a marker of systemic lipid peroxidation (P<0.05). These results provide the first evidence that normotensive subjects with ECG-LVH exhibit defective nitric oxide production, along with increased oxidative stress. Our findings may thus explain, at least in part, a potential mechanism underlying the increased risk of cardiovascular death in normotensive individuals with ECG-LVH.

Progression of Tokyo Guidelines and Japanese Guidelines for management of acute cholangitis and cholecystitis.

The Japanese Guidelines for management of acute cholangitis and cholecystitis were published in 2005 as the first practical guidelines presenting diagnostic and severity assessment criteria for these diseases. After the Japanese version, the Tokyo Guidelines (TG07) were reported in 2007 as the first international practical guidelines. There were some differences between the two guidelines, and some weak points in TG07 were pointed out, such as low sensitivity for diagnosis and the presence of divergence between severity assessment and clinical judgment for acute cholangitis. Therefore, revisions were started to not only make them up to date but also concurrent with the same diagnostic and severity assessment criteria. The Revision Committee for the revision of TG07 (TGRC) performed validation studies of TG07 and new diagnostic and severity assessment criteria of acute cholangitis and cholecystitis. These were retrospective multi-institutional studies that collected cases of acute cholangitis, cholecystitis, and non-inflammatory biliary disease. TGRC held 35 meetings as well as international email exchanges with co-authors abroad and held three International Meetings. Through these efforts, TG13 improved the diagnostic sensitivity for acute cholangitis and cholecystitis, and presented criteria with extremely low false positive rates. Furthermore, severity assessment criteria adapted for clinical use, flowcharts, and many new diagnostic and therapeutic modalities were presented. The world's first management bundles of acute cholangitis and cholecystitis were also presented. The revised Japanese version was published with the same content as TG13. An electronic application of TG13 that can help to diagnose and assess the severity of these diseases using the criteria of TG13 was made for free download.

A rare case of myocardial infarction related to diagnostic intravascular ultrasound.

A 71-year-old man underwent intracoronary stent implantation for acute inferior myocardial infarction (MI). Immediately after diagnostic intravascular ultrasound (IVUS) at 8 months' follow-up, an acute occlusion of the sinus node (SN) artery appeared, which developed sinus arrest with junctional escape rhythm. The serum level of high-sensitivity troponin T (TpT) was markedly elevated on the day after the procedure (2.1-32.5 ng/l), which was indicative of MI related to IVUS. Under continuous intravenous infusion of unfractionated heparin, the escape rhythm changed to lower atrial rhythm on the 4th day, and recovered to sinus rhythm on the 14th day. Coronary angiography (CAG) on 15th day showed a recanalization of the SN artery, but optical coherence tomography identified that disrupted plaque and white thrombus still existed in the ostium of the SN artery. The patient was discharged on maintenance anticoagulation therapy. We hypothesized from this case that IVUS-related myocardial injury may exist without clinical problems. Our retrospective investigation showed that the median levels of high-sensitivity TpT in 20 patients who underwent CAG and subsequent diagnostic IVUS significantly increased from 0.6 (interquartile range 0.3-1.1) to 1.6 (0.7-3.6) ng/l (P < 0.05), suggesting that IVUS may induce very low levels of myocardial injury. In conclusion, we experienced a rare case of IVUS-related MI caused by an acute occlusion of the SN artery. This case reaffirms that we should pay more attention to manipulation of IVUS catheters.

Coronary arterial remodeling and out-stent plaque change after drug-eluting stent implantation--comparison between zotarolimus-eluting stents and paclitaxel-eluting stents.

BACKGROUND: Out-stent plaque characteristics and eosinophilic inflammatory response, which correlates with positive remodeling after first-generation drug-eluting stent implantation, may be associated with late restenosis and very late stent thrombosis. The differences of out-stent plaque characteristics were compared between paclitaxel-eluting stents (PES) and zotarolimus-eluting stents (ZES), using integrated backscatter-intravascular ultrasound (IB-IVUS). METHODS AND RESULTS: Of 78 patients enrolled, 25 receiving PES and 25 receiving ZES had adequate IVUS assessment. Volumetric IVUS analysis was performed after stenting and at 8-month follow-up. Out-stent plaque change in the stented segment was compared on IB-IVUS. The relationship between systemic inflammatory response and out-stent plaque change was evaluated. In PES, vessel volume significantly increased (365-389 mm(3), P<0.0001), whereas it did not change in ZES (315-314 mm(3), P=0.81). In culprit lesions at baseline in PES, fibrous plaque tended to increase (3.1-3.6mm(2), P=0.051) and lipid plaque significantly increased (4.3-5.1mm(2), P=0.02), whereas in ZES the fibrous plaque significantly increased (2.9-4.0mm(2), P<0.0001) but lipid plaque significantly decreased (5.1-3.6mm(2), P<0.0001). Systemic eosinophil increase was significantly correlated with positive remodeling and out-stent lipid plaque increase. CONCLUSIONS: Chronic out-stent plaque change in ZES consisted of less positive remodeling and more favorable effects on out-stent plaque characteristics than PES. Systemic eosinophil change might be a marker of out-stent lipid plaque change.

Association of seasonal variation in the prevalence of metabolic syndrome with insulin resistance.

The aim of this study was to examine the hypothesis that seasonal variation in the prevalence of metabolic syndrome (MetS) is associated with increased insulin resistance. Among 840 Japanese male workers who were evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR) in June (summer) 2010, we prospectively studied a total of 758 subjects (40-65 years of age) who underwent an assessment in December (winter) 2010. MetS was defined according to the criteria proposed by the International Diabetes Federation (IDF) and the Japanese Society of Internal Medicine (JSIM). The median level of HOMA-IR in the study subjects was 0.84 (interquartile range: 0.60-1.19). The prevalence rates of IDF- and JSIM-MetS significantly increased from 12.4 and 9.6% in the summer to 16.6 and 13.3% in the winter, respectively (each P<0.05). Our data suggest that these increases are mainly due to increases in blood pressure (BP) and glucose during the winter assessment. The prevalence rates of IDF-MetS in the first, second, third and fourth quartiles of HOMA-IR were 1.1, 5.8, 14.3 and 29.1% in the summer and 3.1, 10.6, 21.9, and 31.3% in the winter, respectively. Similar results were obtained when using the JSIM criteria. In the third quartile, the frequency of elevated BP increased from 42.4% in the summer to 61.2% in the winter (P<0.05), and these values were mainly correlated with significant variations in IDF- and JSIM-MetS prevalence rates. This study demonstrates that seasonal variation in MetS prevalence is associated with mildly to moderately increased insulin resistance in middle-aged Japanese men.

Successful coronary intervention for spontaneous coronary dissection in a patient with fibromuscular dysplasia.

Spontaneous coronary artery dissection (SCAD) is a reported rare cause of acute coronary syndrome (ACS) and sudden death among middle-aged women. Some institutes have recently reported fibromuscular dysplasia (FMD) concomitant with SCAD. Therefore, a survey of the presence of comorbid FMD in SCAD patients is important to obtain a definitive diagnosis and for the prediction of possible SCAD recurrence. The optimal treatment of ACS due to SCAD remains undetermined, and technical failures are frequently encountered in primary percutaneous coronary intervention (PCI) owing to the unusual non-atherosclerotic cause of the disease. We report a case of SCAD successfully treated with cutting balloon PCI under intravascular ultrasound guidance without stent implantation, in which FMD was detected in the right external iliac artery through screening by noncoronary angiography, not duplex ultrasound. .

Proposed cutoff level of waist circumference in Japanese men: evaluation by homeostasis model assessment of insulin resistance levels.

OBJECTIVE: The aim of this study is to propose the cutoff level of waist circumference (WC) on the basis of homeostasis model assessment of insulin resistance (HOMA-IR) levels in order to diagnose metabolic syndrome (MetS). METHODS: We examined a total of 798 non-diabetic men (40-65 years of age) by using a receiver operating characteristic (ROC) curve to determine the cutoff level that yielded the maximum sensitivity plus specificity. According to the criteria proposed by the International Diabetes Federation (IDF), and the Japanese Society of Internal Medicine (JSIM), subjects with ≥ 2 metabolic components other than abdominal obesity, were considered to have MetS. RESULTS: The overall prevalence rates of IDF- and JSIM-MetS were 17.4% (n=139) and 15.5% (n=124), respectively. The median levels of WC and HOMA-IR were 83.1 [interquartile range (IQR): 78.5-88.4] cm and 0.84 (IQR: 0.61-1.19), respectively. HOMA-IR was highly correlated with each metabolic parameter (each p<0.05), and in addition, multiple linear regression analysis of HOMA-IR (adjusted R2=0.459) showed that WC level was the strongest independent predictors of HOMA-IR level (F=141.1, p<0.05). According to ROC curve analysis, the cutoff level of HOMA-IR for predicting IDF- and JSIM-MetS was 0.92 for both (sensitivity: 79.9% and 78.2%, specificity: 64.9% and 63.6%). Based on the HOMA-IR level, the proposed WC cutoff level was 82.7 cm (sensitivity: 75.4%, specificity: 63.8%). CONCLUSION: This study suggests that WC level should be more strictly managed than current criteria, for preventing the development of MetS in non-diabetic middle-aged Japanese men.

Evaluation of in-stent neointimal tissue components using integrated backscatter intravascular ultrasound: comparison of drug-eluting stents and bare-metal stents.

Although in-stent restenosis (ISR) occurs after drug-eluting stents (DES) implantation, neointimal tissue characteristics have not been fully investigated. We assessed neointimal tissue components using integrated backscatter intravascular ultrasound (IB-IVUS) after DES and bare-metal stents (BMS) implantation. Fifty-seven consecutive patients with 61 lesions underwent repeated percutaneous coronary intervention (PCI) for the treatment of ISR (DES: 24 lesions, BMS: 37 lesions). PCI was performed using plain old balloon angioplasty (POBA). Before PCI, we assessed neointimal tissue characteristics using IB-IVUS. Neointima was divided into four categories: category 1 (-11 to -29 dB), category 2 (-29 to -35 dB), category 3 (-35 to -49 dB), and category 4 (-49 to -130 dB) according to IB values. We compared neointimal tissue components between DES and BMS. Thirty-three patients with 33 lesions (DES: 17, BMS: 16) were finally included. Neointima was predominantly composed of category 3 tissue in both groups (DES: 68 ± 8%, BMS: 73 ± 5%, P = 0.053). DES had a broader distribution of category 4 tissue component than BMS. After POBA, distal slow flow phenomenon occurred in 5 of DES (29%), whereas none of BMS. In DES, the optimal threshold of category 4 tissue to predict distal slow flow phenomenon after POBA was 30% (sensitivity: 100%, specificity: 92%). Neointima was mainly composed of category 3 tissue at ISR site, irrespective of DES or BMS. In DES, there was a subgroup with category 4 rich tissue, which caused distal slow flow phenomenon after POBA. IB-IVUS might be useful to identify vulnerable neointima in DES restenosis.

Intravascular ultrasound and histopathological observations in a patient with very late sirolimus-eluting stent thrombosis.

This case report describes an autopsy case of very late stent thrombosis, which was associated with intravascular ultrasound findings of late-acquired stent malapposition with thrombotic materials and marked positive vascular remodeling at the site of the sirolimus-eluting stent implantation. Histopathological examination showed both destructive and proliferative reactions had occurred in the same stented coronary arterial wall 44 months after sirolimus-eluting stent implantation. Long-lasting severe local inflammation beyond healing reaction, causing vessel enlargement, may be related to very late stent thrombosis.

Elevated depressive symptoms are associated with hypertriglyceridemia in Japanese male workers.

OBJECTIVE: The aim of this study was to determine whether elevated depressive symptoms are associated with metabolic syndrome and its components in the Japanese population. METHODS: Out of 1,386 male workers who underwent measurements of variables of metabolic syndrome components in their health checkup, 1,186 subjects (44.5 ± 9.6 years) completed the Zung self-rating depression scale (ZSDS) (response rate 85.6%). In this study, metabolic syndrome was defined according to the joint scientific statement proposed by 6 major organizations, including the International Diabetes Federation. RESULTS: The overall frequency of elevated depressive symptoms (ZSDS scores ≥40) was 42.1% (n=499). The incidence of metabolic syndrome was significantly higher in subjects with elevated depressive symptoms than in those without (13.2% vs. 8.9%, p<0.05). Of all the metabolic syndrome components, mean triglyceride levels were significantly higher in subjects with elevated depressive symptoms than in those without [124.7 (95% confidence interval (CI): 117.8-131.7) mg/dL vs. 111.5 (95% CI: 107.2-115.9) mg/dL, p<0.05]. Consequently, hypertriglyceridemia (28.9% vs. 21.0%, p<0.01) was the main component correlated with the between-group difference of metabolic syndrome incidence. In the logistic regression analysis after adjustment for potential confounders, the odds ratio of the total ZSDS scores for the diagnosis of hypertriglyceridemia was 1.52 (95% CI: 1.13-2.04; p<0.01), and the major depressive symptom was psychomotor agitation (odds ratio: 1.47; 95% CI: 1.10-1.94; p<0.01). CONCLUSION: This study showed that elevated depressive symptoms were associated with hypertriglyceridemia in Japanese male workers, which affected the clinical diagnosis of metabolic syndrome.

A direct measurement for LDL-cholesterol increases hypercholesterolemia prevalence: comparison with Friedewald calculation.

Direct measurement by homogenous assays has recently been applied to measuring low-density lipoprotein-cholesterol (LDL-C) and has replaced the Friedewald calculation in Japan, but it remains unclear how direct measurement compares with the Friedewald calculation in evaluating hypercholesterolemia. The aim of this study was to determine the effect of the two methods on the diagnosis of hypercholesterolemia. In a total of 1655 workers from our institution (1451 men, 43.6 +/- 10.2 years; 204 women, 38.3 +/- 10.4 years), we investigated the LDL-C levels by the direct and Friedewald methods. In this study, we excluded workers whose triglyceride levels exceeded 400 mg/dl (n=18). Direct LDL-C showed a significantly positive correlation with Friedewald LDL-C (R2 = 0.975, P < 0.0001). On the other hand, the mean direct LDL-C was 5.9 mg/dl higher than the mean Friedewald LDL-C (126.7 +/- 30.6 mg/dl vs. 120.8 +/- 30.5 mg/dl, P < 0.0001), and direct LDL-C was higher in 89.1% of the study population. The frequency of study subjects diagnosed with hypercholesterolemia, defined as LDL-C > or =140 mg/dl, was significantly higher in the direct measurement than in the Friedewald calculation (31.7% vs. 25.1%, P < 0.0001). In conclusion, we demonstrated that the direct measurement showed a higher rate of hypercholesterolemia prevalence than the Friedewald calculation indicated. This result suggests that we have to give careful consideration to the method for measuring LDL-C in the clinical diagnosis and management decisions of hypercholesterolemia.

Seasonal variation in metabolic syndrome prevalence.

Accumulating evidence has shown that seasonal variations can exist within metabolic syndrome parameters. The aim of this study was to examine the hypothesis that there are seasonal variations in the prevalence of metabolic syndrome in Japanese subjects. We investigated a total of 1202 male workers in our institution (44+/-10 years) who underwent health checkups in both June (summer) and December (winter) 2008. In this study, metabolic syndrome was defined according to the criteria proposed by the National Cholesterol Education Program (NCEP), the International Diabetes Federation (IDF) and the Japanese Society of Internal Medicine (JSIM). Serum levels of high-density lipoprotein-cholesterol and fasting glucose, as well as blood pressure (BP), were significantly higher in winter than in summer, whereas waist circumference and serum levels of triglyceride exhibited little change. The prevalence rates of NCEP, IDF, and JSIM metabolic syndrome in this study were 3.8, 15.1 and 12.4% in winter and 3.2, 10.7 and 8.4% in summer, respectively. Of all metabolic syndrome components, an elevated BP was most significantly correlated with the seasonal variation of metabolic syndrome prevalence. This study demonstrated seasonal variations in metabolic syndrome prevalence in Japanese male workers. These results indicate that the season of health checkups may affect the clinical diagnosis and management of metabolic syndrome.

Seasonal variation in serum lipid levels in Japanese workers.

AIM: Seasonal variation in serum lipid levels in the Japanese population remains unclear. The aim of this study was to determine whether a variation in lipid levels exists in Japanese workers. METHODS: We investigated 1,331 employees in our institution (1,192 men, 44+/-10 years; 139 women, 38+/-11 years) who underwent health checkups in both June (summer) and December (winter), 2008. RESULTS: Serum levels of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglyceride were significantly higher in winter than in summer (129.1+/-31.2 mg/dL versus 125.2+/-30.2 mg/dL, p<0.0001; 65.9+/-16.8 mg/dL versus 63.5+/-16.1 mg/dL, p<0.0001; 110.4+/-67.5 mg/dL versus 107.5+/-70.4 mg/dL, p<0.05; respectively), although the ratio of LDL to HDL cholesterol was comparable (2.11+/-0.81 in summer versus 2.12+/-0.81 in winter). The frequency of study subjects diagnosed with hypercholesterolemia, defined as LDL cholesterol > or = 140 mg/dL, was significantly higher in winter than in summer (34.5 % versus 30.9 %, p<0.0001). CONCLUSION: In Japanese workers, we demonstrated that there is a seasonal variation in serum lipid levels and the prevalence of hypercholesterolemia. This result indicates that we have to give careful consideration to the season of blood sampling in the clinical diagnosis of and management decisions for hypercholesterolemia.

A case of familial spontaneous pneumothorax.

We experienced a case of familial spontaneous pneumothorax (SP) without apparent underlying connective tissue disease. A 30-year-old man was referred to our hospital complaining of slight dyspnea and right chest pain due to recurrent SP. The patient had two episodes of primary SP of the right lung, and received chest tube drainage, pleurodesis and surgical bullectomy. Otherwise, his father and two elder sisters also had relapsed primary SP in spite of recurrent prevention therapies. This transmission pattern of the disease phenotype suggested an autosomal dominant inheritance. There have been improvements in pathogenesis, diagnostic procedures and recurrence prevention therapies, but this familial case still suffers from recurrent SP. This familial case may strongly require a new therapeutic strategy for familial SP.

Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 correlates with oxidative stress markers in stable coronary artery disease.

BACKGROUND: Although serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) is reported to be associated with acute coronary syndrome (ACS), its correlation with oxidative stress markers has not been elucidated. We therefore investigated the association of serum sLOX-1 with the severity of CAD, and serum biomarkers for oxidative stress and inflammation, as well as extracellular superoxide dismutase (EC-SOD), which is protective against oxidative stress in the vascular wall. METHODS AND RESULTS: Ninety-four patients with stable CAD were enrolled in this study. Serum sLOX-1, serum high-sensitivity C-reactive protein (hs-CRP), urinary 8-isoprostane, plasma BNP and serum lipid levels were measured. We also measured EC-SOD at baseline and post-heparin injection. Heparin-released EC-SOD (DeltaEC-SOD) was calculated as the difference between these two values. No significant correlation was found between log (sLOX-1) and log (basal EC-SOD) (p=0.096), log (hs-CRP) (p=0.108), or log (BNP) (p=0.908) levels, log (sLOX-1) had a significant correlation with DeltaEC-SOD (r=-0.325, p=0.0014) levels and urinary 8-isoprostane levels (r=0.243, p=0.020). In the multivariable analysis, DeltaEC-SOD (p=0.0177) and 8-isoprostane (p=0.0318) were independent predictors for log (sLOX-1). CONCLUSION: Serum sLOX-1 levels were positively correlated with urinary 8-isoprostane levels and inversely correlated with EC-SOD levels. These results thus suggest that increased serum sLOX-1 levels may reflect enhanced oxidative stress in vascular walls.

Derivatives of reactive oxygen metabolites correlates with high-sensitivity C-reactive protein.

AIM: High-sensitivity C-reactive protein (hsCRP) is a predictor of cardiovascular events. Although oxidative stress may also be related to cardiovascular disease, there are few studies comparing the two. We therefore examined the association of hsCRP, serum lipids, and derivatives of reactive oxygen metabolites (D-ROMs) in coronary artery disease. METHODS: We measured the levels of serum lipids, hsCRP, plasma brain natriuretic peptides (BNP) and D-ROMs in 131 consecutive patients undergoing cardiac catheterization. We divided these subjects into three groups according to their levels of hsCRP. RESULTS: In group C (hsCRP>3.0 mg/L), mean levels of serum D-ROMs were significantly higher than in groups A (hsCRP<1.0 mg/L) and B (hsCRP 1.0 to 3.0 mg/L). Serum levels of D-ROMs and log (hsCRP) correlated in the total population (r=0.479, p<0.0001), and D-ROMs, HDL-C, LDL-C and log-transformed plasma BNP were independent predictors of hsCRP (p<0.0001). CONCLUSION: We concluded that oxidative stress increases in patients at high risk for cardiovascular events based on their hsCRP.

Gene transfer of extracellular superoxide dismutase ameliorates pulmonary hypertension in rats.

RATIONALE: Pulmonary hypertension (PH) is a life-threatening disease, characterized by vascular remodeling and vasoconstriction. Evidence suggests that oxidative stress may contribute to the pathogenesis and/or development of PH. OBJECTIVES: In the present study, we examined whether intratracheal gene transfer of human extracellular superoxide dismutase (EC-SOD) could ameliorate monocrotaline (MCT)-induced PH in rats. METHODS: MCT-injected rats were intratracheally administered vehicle (MCT group) or an adenovirus encoding beta-galactosidase (Adbetagal group) or human EC-SOD (AdEC-SOD group). MEASUREMENTS AND MAIN RESULTS: After intratracheal gene transfer, EC-SOD was successfully expressed in lung tissue, bronchoalveolar lavage fluid, and plasma. Twenty-eight days after MCT injection, right ventricular systolic pressure and the weight ratio of the right ventricle to the left ventricle plus septum were significantly lower in the AdEC-SOD group (42.50 +/- 1.46 mm Hg and 0.453 +/- 0.029, respectively) than in the MCT group (59.89 +/- 1.61 mm Hg and 0.636 +/- 0.022, respectively) or the Adbetagal group (61.50 +/- 2.61 mm Hg and 0.653 +/- 0.038, respectively). Moreover, vascular remodeling and proliferation of vascular smooth muscle cells in pulmonary arteries were markedly suppressed in the AdEC-SOD group. Importantly, 8-isoprostane in lung tissue was also significantly reduced in the AdEC-SOD group. CONCLUSIONS: EC-SOD overexpression to the lung ameliorated MCT-induced PH in rats. We suggest that EC-SOD may act as an antioxidant in PH and that increased oxidative stress may be important in the pathogenesis of MCT-induced PH.

Angiotensin receptor blocker improves coronary flow velocity reserve in hypertensive patients: comparison with calcium channel blocker.

Large-scale clinical studies have indicated that angiotensin receptor blockers (ARBs) have beneficial effects against cardiovascular diseases. We designed this study to compare the effects of an ARB and a calcium channel blocker (CCB) on coronary flow velocity reserve (CFVR), a predictor of cardiovascular events, as estimated using transthoracic Doppler echocardiography. Sixteen hypertensive patients (63.1+/-9.6 years old; 10 males) were randomly allocated in a double-blind fashion to valsartan (n=8, 40-80 mg/day) or nifedipine (n=8, 20-40 mg/day) groups. Age- and gender-matched subjects without hypertension were enrolled as a control group (n=12). CFVR was calculated by dividing the adenosine triphosphate-induced hyperemic flow velocity by the basal flow velocity in the left anterior descending coronary artery. Baseline characteristics and reduction in systolic and diastolic blood pressure after 6 months were similar in both groups. CFVR in the valsartan group increased from 2.34+/-0.38 to 3.10+/-0.84 at 2 months (p<0.05), and to 3.04+/-1.09 at 6 months (p<0.01). Both values became comparable to that in the control group (2.81+/-0.60). CFVR in the valsartan group was significantly higher (p<0.001) than that in the nifedipine group, which was little changed at 6 months. This discrepancy was derived from the significant increase of hyperemic velocity in the valsartan group, from 36.6+/-17.3 cm/s to 41.1+/-12.7 cm/s at 2 months, and to 48.1+/-20.2 cm/s at 6 months. We concluded that the ARB valsartan not only reduced high blood pressure but improved CFVR in hypertensive patients. However, these effects were not seen with the CCB nifedipine.